Programmed cell death protein 6

Details

Name
Programmed cell death protein 6
Synonyms
  • ALG2
  • Apoptosis-linked gene 2 protein
  • Probable calcium-binding protein ALG-2
Gene Name
PDCD6
Organism
Humans
Amino acid sequence
>lcl|BSEQ0009841|Programmed cell death protein 6
MAAYSYRPGPGAGPGPAAGAALPDQSFLWNVFQRVDKDRSGVISDTELQQALSNGTWTPF
NPVTVRSIISMFDRENKAGVNFSEFTGVWKYITDWQNVFRTYDRDNSGMIDKNELKQALS
GFGYRLSDQFHDILIRKFDRQGRGQIAFDDFIQGCIVLQRLTDIFRRYDTDQDGWIQVSY
EQYLSMVFSIV
Number of residues
191
Molecular Weight
21868.32
Theoretical pI
Not Available
GO Classification
Functions
binding, bridging / calcium ion binding / calcium-dependent cysteine-type endopeptidase activity / calcium-dependent protein binding / identical protein binding / protein anchor / protein dimerization activity
Processes
activation of cysteine-type endopeptidase activity involved in apoptotic process / angiogenesis / apoptotic signaling pathway / cellular response to heat / intracellular protein transport / negative regulation of protein kinase B signaling / negative regulation of TOR signaling / negative regulation of vascular endothelial growth factor receptor signaling pathway / positive regulation of angiogenesis / positive regulation of cysteine-type endopeptidase activity involved in apoptotic process / positive regulation of endothelial cell migration / positive regulation of endothelial cell proliferation / proteolysis / response to calcium ion / vascular endothelial growth factor receptor-2 signaling pathway
Components
cytoplasm / cytoplasmic vesicle / endoplasmic reticulum / endoplasmic reticulum exit site / endoplasmic reticulum membrane / endosome / extracellular exosome / nuclear membrane / nucleus
General Function
Protein dimerization activity
Specific Function
Calcium-binding protein required for T-cell receptor-, Fas-, and glucocorticoid-induced cell death. May mediate Ca(2+)-regulated signals along the death pathway (By similarity). Calcium-dependent adapter necessary for the association between PDCD6IP and TSG101. Interaction with DAPK1 can accelerate apoptotic cell death by increasing caspase-3 activity. May inhibit KDR/VEGFR2-dependent angiogenesis; the function involves inhibition of VEGF-induced phosphoprylation of the Akt signaling pathway. Seems to play a role in the regulation of the distribution and function of MCOLN1 in the endosomal pathway. Isoform 2 has a lower Ca(2+) affinity than isoform 1. Isoform 1 and, to a lesser extend, isoform 2, can stabilize SHISA5.
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Nucleus membrane
Gene sequence
>lcl|BSEQ0017845|Programmed cell death protein 6 (PDCD6)
ATGGCCGCCTACTCTTACCGCCCCGGCCCTGGGGCCGGCCCTGGGCCTGCTGCAGGCGCG
GCGCTGCCGGACCAGAGCTTCCTGTGGAACGTTTTCCAGAGGGTCGATAAAGACAGGAGT
GGAGTGATATCAGACACCGAGCTTCAGCAAGCTCTCTCCAACGGCACGTGGACTCCCTTT
AATCCAGTGACTGTCAGGTCGATCATATCCATGTTTGACCGTGAGAACAAGGCCGGCGTG
AACTTCAGCGAGTTCACGGGTGTGTGGAAGTACATCACGGACTGGCAGAACGTCTTCCGC
ACGTACGACCGGGACAACTCCGGGATGATCGATAAGAACGAGCTGAAGCAGGCCCTCTCA
GGCTACCGGCTCTCTGACCAGTTCCACGACATCCTCATTCGAAAGTTTGACAGGCAGGGA
CGGGGGCAGATTGCCTTCGACGACTTCATCCAGGGCTGCATCGTCCTGCAGAGGTTGACG
GATATATTCAGACGTTACGACACGGATCAGGACGGCTGGATTCAGGTGTCGTACGAACAG
TACCTGTCCATGGTCTTCAGTATCGTATGA
Chromosome Location
5
Locus
Not Available
External Identifiers
ResourceLink
UniProtKB IDO75340
UniProtKB Entry NamePDCD6_HUMAN
HGNC IDHGNC:8765
General References
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  4. Kitaura Y, Matsumoto S, Satoh H, Hitomi K, Maki M: Peflin and ALG-2, members of the penta-EF-hand protein family, form a heterodimer that dissociates in a Ca2+-dependent manner. J Biol Chem. 2001 Apr 27;276(17):14053-8. Epub 2001 Feb 1. [PubMed:11278427]
  5. Kitaura Y, Satoh H, Takahashi H, Shibata H, Maki M: Both ALG-2 and peflin, penta-EF-hand (PEF) proteins, are stabilized by dimerization through their fifth EF-hand regions. Arch Biochem Biophys. 2002 Mar 1;399(1):12-8. [PubMed:11883899]
  6. Satoh H, Shibata H, Nakano Y, Kitaura Y, Maki M: ALG-2 interacts with the amino-terminal domain of annexin XI in a Ca(2+)-dependent manner. Biochem Biophys Res Commun. 2002 Mar 15;291(5):1166-72. [PubMed:11883939]
  7. Lee JH, Rho SB, Chun T: Programmed cell death 6 (PDCD6) protein interacts with death-associated protein kinase 1 (DAPk1): additive effect on apoptosis via caspase-3 dependent pathway. Biotechnol Lett. 2005 Jul;27(14):1011-5. [PubMed:16132846]
  8. Montaville P, Dai Y, Cheung CY, Giller K, Becker S, Michalak M, Webb SE, Miller AL, Krebs J: Nuclear translocation of the calcium-binding protein ALG-2 induced by the RNA-binding protein RBM22. Biochim Biophys Acta. 2006 Nov;1763(11):1335-43. Epub 2006 Sep 14. [PubMed:17045351]
  9. Yamasaki A, Tani K, Yamamoto A, Kitamura N, Komada M: The Ca2+-binding protein ALG-2 is recruited to endoplasmic reticulum exit sites by Sec31A and stabilizes the localization of Sec31A. Mol Biol Cell. 2006 Nov;17(11):4876-87. Epub 2006 Sep 6. [PubMed:16957052]
  10. Draeby I, Woods YL, la Cour JM, Mollerup J, Bourdon JC, Berchtold MW: The calcium binding protein ALG-2 binds and stabilizes Scotin, a p53-inducible gene product localized at the endoplasmic reticulum membrane. Arch Biochem Biophys. 2007 Nov 1;467(1):87-94. Epub 2007 Aug 21. [PubMed:17889823]
  11. Shibata H, Suzuki H, Kakiuchi T, Inuzuka T, Yoshida H, Mizuno T, Maki M: Identification of Alix-type and Non-Alix-type ALG-2-binding sites in human phospholipid scramblase 3: differential binding to an alternatively spliced isoform and amino acid-substituted mutants. J Biol Chem. 2008 Apr 11;283(15):9623-32. doi: 10.1074/jbc.M800717200. Epub 2008 Feb 6. [PubMed:18256029]
  12. Okumura M, Ichioka F, Kobayashi R, Suzuki H, Yoshida H, Shibata H, Maki M: Penta-EF-hand protein ALG-2 functions as a Ca2+-dependent adaptor that bridges Alix and TSG101. Biochem Biophys Res Commun. 2009 Aug 14;386(1):237-41. doi: 10.1016/j.bbrc.2009.06.015. Epub 2009 Jun 9. [PubMed:19520058]
  13. Vergarajauregui S, Martina JA, Puertollano R: Identification of the penta-EF-hand protein ALG-2 as a Ca2+-dependent interactor of mucolipin-1. J Biol Chem. 2009 Dec 25;284(52):36357-66. doi: 10.1074/jbc.M109.047241. Epub 2009 Oct 28. [PubMed:19864416]
  14. Burkard TR, Planyavsky M, Kaupe I, Breitwieser FP, Burckstummer T, Bennett KL, Superti-Furga G, Colinge J: Initial characterization of the human central proteome. BMC Syst Biol. 2011 Jan 26;5:17. doi: 10.1186/1752-0509-5-17. [PubMed:21269460]
  15. Janowicz A, Michalak M, Krebs J: Stress induced subcellular distribution of ALG-2, RBM22 and hSlu7. Biochim Biophys Acta. 2011 May;1813(5):1045-9. doi: 10.1016/j.bbamcr.2010.11.010. Epub 2010 Nov 29. [PubMed:21122810]
  16. Rho SB, Song YJ, Lim MC, Lee SH, Kim BR, Park SY: Programmed cell death 6 (PDCD6) inhibits angiogenesis through PI3K/mTOR/p70S6K pathway by interacting of VEGFR-2. Cell Signal. 2012 Jan;24(1):131-9. doi: 10.1016/j.cellsig.2011.08.013. Epub 2011 Aug 26. [PubMed:21893193]
  17. Bienvenut WV, Sumpton D, Martinez A, Lilla S, Espagne C, Meinnel T, Giglione C: Comparative large scale characterization of plant versus mammal proteins reveals similar and idiosyncratic N-alpha-acetylation features. Mol Cell Proteomics. 2012 Jun;11(6):M111.015131. doi: 10.1074/mcp.M111.015131. Epub 2012 Jan 5. [PubMed:22223895]
  18. Vaca Jacome AS, Rabilloud T, Schaeffer-Reiss C, Rompais M, Ayoub D, Lane L, Bairoch A, Van Dorsselaer A, Carapito C: N-terminome analysis of the human mitochondrial proteome. Proteomics. 2015 Jul;15(14):2519-24. doi: 10.1002/pmic.201400617. Epub 2015 Jun 8. [PubMed:25944712]
  19. Suzuki H, Kawasaki M, Inuzuka T, Okumura M, Kakiuchi T, Shibata H, Wakatsuki S, Maki M: Structural basis for Ca2+ -dependent formation of ALG-2/Alix peptide complex: Ca2+/EF3-driven arginine switch mechanism. Structure. 2008 Oct 8;16(10):1562-73. doi: 10.1016/j.str.2008.07.012. [PubMed:18940611]
  20. Inuzuka T, Suzuki H, Kawasaki M, Shibata H, Wakatsuki S, Maki M: Molecular basis for defect in Alix-binding by alternatively spliced isoform of ALG-2 (ALG-2DeltaGF122) and structural roles of F122 in target recognition. BMC Struct Biol. 2010 Aug 6;10:25. doi: 10.1186/1472-6807-10-25. [PubMed:20691033]
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Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB11093Calcium Citrateapproved, investigationalunknownagonistDetails
DB11348Calcium PhosphateapprovedunknownagonistDetails
DB01373Calciumapproved, nutraceuticalunknownDetails
DB01593Zincapproved, investigationalunknownDetails
DB14481Calcium phosphate dihydrateapprovedunknownDetails
DB14487Zinc acetateapproved, investigationalunknownDetails
DB14533Zinc chlorideapproved, investigationalunknownDetails